Sertraline Delivered in Phosphatidylserine Liposomes Is Effective in an Experimental Model of Visceral Leishmaniasis

Author(s)

Romanelli, Maiara Maria ^[1] ; da Costa-Silva, Thais Alves ^[1] ; Cunha-Junior, Edezio ^[2] ; Dias Ferreira, Daiane ^[1] ; Guerra, Juliana M. ^[3] ; Galisteo, Jr., Andres Jimenez ^[4] ; Pinto, Erika Gracielle ^[5] ; Barbosa, Leandro R. S. ^[6] ; Torres-Santos, Eduardo Caio ^[2] ; Tempone, Andre Gustavo ^[1]

Affiliation

^[1] Adolfo Lutz Inst, Ctr Parasitol & Mycol, Sao Paulo - Brazil

^[2] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Bioquim Tripanosomatideos, Pavilhao Leonidas Deane, Rio De Janeiro - Brazil

^[3] Adolfo Lutz Inst, Ctr Pathol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Sao Paulo - Brazil

^[5] Univ Dundee, Drug Discovery Unit, Life Sci, Dundee - Scotland

^[6] Univ Sao Paulo, Inst Fis, Cidade Univ, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY; v. 9, OCT 29 2019.
• Web of Science Citations: 0

Abstract

Liposomes containing phosphatidylserine (PS) has been used for the delivery of drugs into the intramacrophage milieu. Leishmania (L.) infantum parasites live inside macrophages and cause a fatal and neglected viscerotropic disease, with a toxic treatment. Sertraline was studied as a free formulation (SERT) and also entrapped into phosphatidylserine liposomes (LP-SERT) against intracellular amastigotes and in a murine model of visceral leishmaniasis. LP-SERT showed a potent activity against intracellular amastigotes with an EC50 value of 2.5 mu M. The in vivo efficacy of SERT demonstrated a therapeutic failure. However, when entrapped into negatively charged liposomes (-58 mV) of 125 nm, it significantly reduced the parasite burden in the mice liver by 89% at 1 mg/kg, reducing the serum levels of the cytokine IL-6 and upregulating the levels of the chemokine MCP-1. Histopathological studies demonstrated the presence of an inflammatory infiltrate with the development of granulomas in the liver, suggesting the resolution of the infection in the treated group. Delivery studies showed fluorescent-labeled LP-SERT in the liver and spleen of mice even after 48 h of administration. This study demonstrates the efficacy of PS liposomes containing sertraline in experimental VL. Considering the urgent need for VL treatments, the repurposing approach of SERT could be a promising alternative. (AU)

• FAPESP's process: 18/10279-6 - Selection and Optimization of New Drug Candidates for Leishmaniasis and Chagas Disease
• Grantee: André Gustavo Tempone Cardoso
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/15822-1 - Physicochemical and structural properties of Ionic Liquids and drugs interacting with biologicaly relevant systems.
• Grantee: Leandro Ramos Souza Barbosa
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07275-5 - In vitro study of cellular immune response against synthetic drugs with antileishmanial activities
• Grantee: Thaís Alves da Costa Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/23403-9 - Rational Pre-Clinical Study of New Drug Candidates Against Neglected Protozoan Diseases Using Pharmacokinetic Approaches
• Grantee: André Gustavo Tempone Cardoso
• Support Opportunities: Regular Research Grants